The response to sepsis appears to differ from that seen in other kinds of surgical stress and these differences may be important in survival. The studies described in this application focus on the neuroendocrine and metabolic patterns that characterize such patients and are designed to investigate the hypothesis that catabolism in septic patients is not only more severe but differs in important ways from that seen in nonseptic surgical patients. Nutritional support in such patients continues to be a challenge and the impact of exogenous fuels will be examined. Both whole body and regional techniques will be employed and the goals are to contrast peripheral (extremity) and visceral (splanchnic) metabolism in an effort to localize the abnormalities and investigate the efficacy of supportive measures. Uptake and release of the major substrates and hormones will be quantitated by measurements of flow and A-V differences and, in addition, net protein synthesis, ketogenesis and lipogenesis will be estimated by special techniques. Although this is primarily envisioned as a clinical study more invasive animal experiments will be needed to interpret the individual events that make up splanchnic exchange and to help to interpret the clinical data.